Relapse after treatment for drug dependence is a fundamental problem in the management of this disorder. Despite apparently good initial treatment and strong motivation on the part of the patient to remain abstinent, return to drug use is common. Analysis of the reasons for relapse reveal a complex mix of psychosocial and environmental variables. One class of variable which has not received much attention from treatment programs has been the automatic learning or conditioning which occurs naturally during the course of drug abuse and persists long after the last dose of drugs. With repeated use of a drug, the environmental cues-sights, sounds, smells, situations-involved in obtaining and administering the drug become associated with drug effects or drug withdrawal. This learning is automatic and most patients are unaware that it is happening. However, when subsequently exposed to the drug-related stimuli, the patient may experience feelings of drug withdrawal or drug need without understanding where the feelings come from. While there is evidence from animal studies that opioids, cocaine, amphetamines and alcohol can produce conditioned responses, few studies have been done in human subjects. Two projects are proposed. Cocaine abusers, opioid abusers and those abusing both types of drugs will be studied to determine the nature of the physiological and subjective responses elicited by drug related stimuli. This will build on our prior work which has demonstrated conditioned drug withdrawal and drug craving in opioid dependent persons in response to specific cues. These responses can be measured in the laboratory. We will determine whether there are differences in conditioned responses between cocaine and opioid abusers and whether certain stimuli are more evocative with one type of drug. This information will be used to develop a treatment which modifies or extinguish these responses. Extinction by repeated, gradual exposure to drug-related stimuli in the laboratory has so far been successful in reducing conditioned responses in opioid addicts. The second project involves a continuation of our efforts to incorporate basic laboratory findings into an improved practical treatment package. One study in methadone-maintained opioid addicts has already been completed; a second in abstinent opioid patients is in progress and a third in cocaine-dependent patients is proposed. This experimental therapy aimed at reducing the conditioning factors involved in relapse will be intergrated with a standard treatment program. Using appropriate control groups, the effects of extinction will be measured and compared to efficacy in groups receiving standard treatments, but not extinction.